Associations of particulate matter with atopic dermatitis and chronic inflammatory skin diseases in South Korea.

BACKGROUND: Particulate matter (PM) is a mixture of solid and liquid particles suspended in air, which originates from industrial plants or vehicle emissions. Although the skin is the primary body area of contact with air pollutants, the associations between PM and chronic inflammatory skin diseases has not been well established. AIM: To investigate associations between PM and atopic dermatitis (AD) and between PM and other chronic inflammatory dermatoses, using data from the Korean Health Insurance Review and Assessment Service. METHODS: Monthly disease statistics from the seven largest cities in South Korea (Seoul, Busan, Daegu, Incheon, Gwangju, Daejeon, Ulsan) and from Jeju Island (in total, a population of 23 288 000 for all eight areas) were included. Based on daily air pollution level and weather forecast from 2015 to 2019, multivariate negative binomial regression analysis was conducted to estimate monthly visits of AD with respect to outdoor air pollutants: coarse PM with a diameter of ≤ 10 µm (PM10) and fine PM with a diameter of ≤ 2.5 µm (PM2.5) ozone (O3 ), nitrogen dioxide (NO2 ), sulphur dioxide (SO2 ) and carbon monoxide (CO). RESULTS: Increases in the levels of PM2.5, PM10, SO2 and CO were associated with significant increases in monthly patient visits for AD. Every 10 µg/m3 increase in PM2.5 and PM10 resulted in patient visit increases of 2.71% (95% CI 0.76-4.71; P < 0.01) and 2.01% (95% CI 0.92-3.11, P < 0.001), respectively, while every 1 part per billion (ppb) increase in SO2 and every 100 ppb increase in CO resulted in visit increases of 2.26% (95% CI 1.35-3.17; P < 0.001) and 2.86% (95% CI 1.35-4.40; P < 0.001), respectively. O3 and NO2 were not associated with increased patient visits for AD. Increases in PM2.5 and PM10 concentrations were also significantly associated with increases in patient visits for psoriasis, seborrhoeic dermatitis and rosacea. CONCLUSION: Our data suggest that PM is associated with AD and other chronic inflammatory skin diseases.

Indocyanine green fluorescence lymphography during gastrectomy after initial endoscopic submucosal dissection for early gastric cancer.

BACKGROUND: Indocyanine green (ICG) fluorescence lymphography can be used to visualize the lymphatic drainage of gastric cancer. Few studies have been performed to identify lymphatic drainage patterns after endoscopic submucosal dissection (ESD). ESD results in changes to lymphatics owing to fibrosis of the submucosal layer. This study aimed to evaluate the efficacy of ICG fluorescence lymphography for visualization of lymphatic drainage after ESD, and to assess its clinical application in additional gastrectomy after ESD for early gastric cancer. METHODS: All patients who underwent gastrectomy after ESD between 2014 and 2017 in a single centre were reviewed. ICG was injected endoscopically into the submucosal layer around the ESD scar the day before surgery. At the time of surgery, lymph nodes (LNs) were visualized and lymphadenectomy was performed with near-infrared imaging. Ex vivo, all LNs were examined for the presence of fluorescence. Number of LNs resected and number of tumour-positive LNs were compared between patients who underwent near-infrared imaging and those who had conventional lymphadenectomy without intraoperative imaging. RESULTS: Some 290 patients underwent gastrectomy after ESD, 98 with fluorescence lymphography-guided lymphadenectomy and 192 with conventional lymphadenectomy. Fluorescence lymphography visualized lymphatic drainage in all patients, without complications related to ICG injection or near-infrared imaging. Fluorescence lymphography visualized all stations containing metastatic LNs. The sensitivity for detecting LN metastasis in fluorescent stations was 100 per cent (9 of 9 stations), and the negative predictive value was 100 per cent (209 of 209). One patient with LN metastasis had one non-fluorescent metastatic LN within a fluorescent station. CONCLUSION: Fluorescence lymphography successfully visualized all draining LNs after ESD, with high sensitivity and negative predictive value for detecting LN metastasis. Fluorescence lymphography-guided lymphadenectomy could be an alternative to systematic lymphadenectomy during additional surgery after ESD.

ANTECEDENTES: La linfografía de fluorescencia con verde de indocianina (indocyanine green, ICG) visualiza el drenaje linfático del cáncer gástrico. Se han realizado pocos estudios para identificar los patrones de drenaje linfático tras una disección submucosa endoscópica (endoscopic submucosal dissection, ESD). La ESD introduce cambios de los linfáticos debido a la fibrosis de la capa submucosa. El objetivo de este estudio era valorar la eficacia de la linfografía con ICG para visualizar el drenaje linfático tras ESD y evaluar su aplicación clínica en la gastrectomía adicional después de ESD por carcinoma precoz gástrico (early gastric cancer, EGC). MÉTODOS: Se revisaron todos los pacientes sometidos a gastrectomía tras ESD entre 2014 y 2017 en un único centro. El ICG se inyectó por vía endoscópica en la capa submucosa alrededor de la cicatriz tras ESD el día antes de la cirugía. En el momento de la cirugía, se visualizaron los ganglios linfáticos (lymph nodes, LNs) y se realizó la linfadenectomía siguiendo las imágenes de infrarrojo. Ex vivo, todos los LNs se examinaron para detectar la presencia de fluorescencia. Se compararon el número de LNs resecados y el número de LNs afectados por el tumor entre pacientes sometidos a imágenes de infrarrojo y pacientes a los que se les realizó una linfadenectomía convencional sin imágenes intraoperatorias. RESULTADOS: Un total de 290 pacientes fueron sometidos a gastrectomía tras ESD (98 con linfadenectomía por linfografía con ICG y 192 con linfadenectomía convencional). La linfografía con ICG visualizó el drenaje linfático en todos los pacientes, sin complicaciones relacionadas con la inyección de ICG o con las imágenes de infrarrojo. La linfografía con ICG permitió visualizar todas las estaciones ganglionares en las que había LNs metastásicos. La sensibilidad para detectar los LN con metástasis en las estaciones con fluorescencia fue del 100% (9 de 9 estaciones), y el valor predictivo negativo (negative predictive value, NPV) del 100% (209 de 209 estaciones). Un paciente con metástasis en LN tenía un ganglio metastásico sin fluorescencia en el seno de una estación con fluorescencia. CONCLUSIÓN: La linfografía con fluorescencia visualiza satisfactoriamente todos los LNs que drenan después de ESD, con una elevada sensibilidad y NPV para detectar metástasis en LN. La linfadenectomía guiada por fluorescencia podría ser una alternativa a la linfadenectomía convencional durante la cirugía adicional después de ESD.

Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma.

BACKGROUND: Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction. METHODS: We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma. RESULTS: Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P<0.001 for all comparisons). At the last spirometric measurement (mean [±SD] age, 26.0±1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P<0.001). CONCLUSIONS: Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.).

Tumor mutational burden is predictive of response to immune checkpoint inhibitors in MSI-high metastatic colorectal cancer.

BACKGROUND: Microsatellite instability (MSI) is a biomarker for response to immune checkpoint inhibitors (ICPIs). PD-1 inhibitors in metastatic colorectal carcinoma (mCRC) with MSI-high (MSI-H) have demonstrated a high disease control rate and favorable progression-free survival (PFS); however, reported response rates to pembrolizumab and nivolumab are variable and often <50%, suggesting that additional predictive biomarkers are needed. METHODS: Clinicopathologic data were collected from patients with MSI-H mCRC confirmed by hybrid capture-based next-generation sequencing (NGS) treated with PD-1/L1 inhibitors at five institutes. Tumor mutational burden (TMB) was determined on 0.8-1.1 Mb of sequenced DNA and reported as mutations/Mb. Potential biomarkers of response and time to progression were analyzed by univariate and multivariate analyses. Once TMB was confirmed as a predictive biomarker, a larger dataset of 18 140 unique CRC patients was analyzed to define the relevance of the identified TMB cut-point. RESULTS: A total of 22 patients were treated with PD-1/L1 inhibitors including 19 with pembrolizumab monotherapy. Among tested variables, TMB showed the strongest association with objective response (OR; P < 0.001) and PFS, by univariate (P < 0.001) and multivariate analysis (P < 0.01). Using log-rank statistics, the optimal predictive cut-point for TMB was estimated between 37 and 41 mutations/Mb. All 13 TMBhigh cases responded, while 6/9 TMBlow cases had progressive disease. The median PFS for TMBhigh has not been reached (median follow-up >18 months) while the median PFS for TMBlow was 2 months. A TMB of 37.4 mutations/Mb in a large MSI-H mCRC population (821/18, 140 cases; 4.5%) evaluated by NGS corresponded to the 35th percentile cut-point. CONCLUSIONS: TMB appears to be an important independent biomarker within MSI-H mCRC to stratify patients for likelihood of response to ICPIs. If validated in prospective studies, TMB may play an important role in guiding the sequencing and/or combinations of ICPIs in MSI-H mCRC.

De novo truncating variants in the intronless IRF2BPL are responsible for developmental epileptic encephalopathy.

PURPOSE: Developmental and epileptic encephalopathies (DEEs) are severe clinical conditions characterized by stagnation or decline of cognitive and behavioral abilities preceded, accompanied or followed by seizures. Because DEEs are clinically and genetically heterogeneous, next-generation sequencing, especially exome sequencing (ES), is becoming a first-tier strategy to identify the molecular etiologies of these disorders. METHODS: We combined ES analysis and international data sharing. RESULTS: We identified 11 unrelated individuals with DEE and de novo heterozygous truncating variants in the interferon regulatory factor 2-binding protein-like gene (IRF2BPL). The 11 individuals allowed for delineation of a consistent neurodevelopmental disorder characterized by mostly normal initial psychomotor development followed by severe global neurological regression and epilepsy with nonspecific electroencephalogram (EEG) abnormalities and variable central nervous system (CNS) anomalies. IRF2BPL, also known as enhanced at puberty protein 1 (EAP1), encodes a transcriptional regulator containing a C-terminal RING-finger domain common to E3 ubiquitin ligases. This domain is required for its repressive and transactivating transcriptional properties. The variants identified are expected to encode a protein lacking the C-terminal RING-finger domain. CONCLUSIONS: These data support the causative role of truncating IRF2BPL variants in pediatric neurodegeneration and expand the spectrum of transcriptional regulators identified as molecular factors implicated in genetic developmental and epileptic encephalopathies.

Gender difference in the impact of coexisting diabetes mellitus on long-term clinical outcome in people with heart failure: a report from the Korean Heart Failure Registry.

AIM: Few data are available on the gender-related differences in the prognostic impact of diabetes in people with heart failure. This study was performed to investigate whether there is a gender difference in the association between diabetes and long-term clinical outcomes in people hospitalized for heart failure. METHODS: A total of 3162 people hospitalized with heart failure (aged 67.4 ± 14.1 years, 50.4% females) from the data set of the nationwide registry were analysed. The primary endpoint was a composite of all-cause mortality and heart failure readmission. RESULTS: People with diabetes (30.5% for males vs. 31.1% for females, P = 0.740) were older and had more unfavourable risk factors and laboratory findings than those without diabetes in both genders. During a median follow-up period of 549 days, there were 1418 cases of composite events (44.8%). In univariable analysis, the coexistence of diabetes was significantly associated with a higher incidence of composite events in both genders (P < 0.05 each for males and females). In multivariable analysis, the prognostic impact of diabetes on the development of composite events remained significant in females even after controlling for potential confounders (hazard ratio 1.43, 95% confidence intervals 1.12-1.84; P = 0.004). However, an independent association between diabetes and composite events was not seen in males in the same multivariable analysis (P > 0.05). CONCLUSIONS: In people with heart failure, the impact of diabetes on long-term mortality and heart failure readmission seems to be stronger in females than in males. More careful and intensive management is needed especially in females with heart failure and diabetes.

Diet-induced obesity leads to metabolic dysregulation in offspring via endoplasmic reticulum stress in a sex-specific manner.

BACKGROUND/OBJECTIVES: Exposure to metabolic stress has been suggested to influence the susceptibility to metabolic disorders in offspring according to epidemiological and animal studies. Nevertheless, molecular mechanisms remain unclear. We investigated impacts of diet-induced paternal obesity on metabolic phenotypes in offspring and its underlying molecular mechanism. SUBJECTS/METHODS: Male founder mice (F0), fed with control diet (CD) or high-fat diet (HFD), were mated with CD-fed females. F1 progenies were mated with outbred mice to generate F2 mice. All offspring were maintained on CD. Metabolic phenotypes, metabolism-related gene expression and endoplasmic reticulum (ER) stress markers were measured in serum or relevant tissues of F2 mice. DNA methylation in sperm and testis of the founder and in the liver of F2 mice was investigated. RESULTS: Male founder obesity, instigated by HFD, led to glucose dysregulation transmitted down to F2. We found that F2 males to HFD founders were overweight and had a high fasting glucose relative to F2 to CD founders. F2 females to HFD founders, in contrast, had a reduced bodyweight relative to F2 to CD founders and exhibited an early onset of impaired glucose homeostasis. The sex-specific difference was associated with distinct transcriptional patterns in metabolism-related organs, showing altered hepatic glycolysis and decreased adipose Glucose transporter 4 (Glut4) in males and increased gluconeogenesis and lipid synthesis in females. Furthermore, the changes in females were linked to hepatic ER stress, leading to suppressed insulin signaling and non-obese hyperglycemic phenotypes. DNA methylation analysis revealed that the Nr1h3 locus was sensitive to HFD at founder germ cells and the alteration was also detected in the liver of F2 female. CONCLUSION: Our findings demonstrate that male founder obesity influences impaired glucose regulation in F2 progeny possibly via ER stress in a sex-specific manner and it is, in part, contributed by altered DNA methylation at the Nr1h3 locus.

Diagnostic exome sequencing in children: A survey of parental understanding, experience and psychological impact.

Clinical exome sequencing (CES) is increasingly being used as an effective diagnostic tool in the field of pediatric genetics. We sought to evaluate the parental experience, understanding and psychological impact of CES by conducting a survey study of English-speaking parents of children who had diagnostic CES. Parents of 192 unique patients participated. The parent's interpretation of the child's result agreed with the clinician's interpretation in 79% of cases, with more frequent discordance when the clinician's interpretation was uncertain. The majority (79%) reported no regret with the decision to have CES. Most (65%) reported complete satisfaction with the genetic counseling experience, and satisfaction was positively associated with years of genetic counselor (GC) experience. The psychological impact of CES was greatest for parents of children with positive results and for parents with anxiety or depression. The results of this study are important for helping clinicians to prepare families for the possible results and variable psychological impact of CES. The frequency of parental misinterpretation of test results indicates the need for additional clarity in the communication of results. Finally, while the majority of patients were satisfied with their genetic counseling, satisfaction was lower for new GCs, suggesting a need for targeted GC training for genomic testing.

Expansion and further delineation of the SETD5 phenotype leading to global developmental delay, variable dysmorphic features, and reduced penetrance.

Diagnostic exome sequencing (DES) has aided delineation of the phenotypic spectrum of rare genetic etiologies of intellectual disability (ID). A SET domain containing 5 gene (SETD5) phenotype of ID and dysmorphic features has been previously described in relation to patients with 3p25.3 deletions and in a few individuals with de novo sequence alterations. Herein, we present additional patients with pathogenic SETD5 sequence alterations. The majority of patients in this cohort and previously reported have developmental delay, behavioral/psychiatric issues, and variable hand and skeletal abnormalities. We also present an apparently unaffected carrier mother of an affected individual and a carrier mother with normal intelligence and affected twin sons. We suggest that the phenotype of SETD5 is more complex and variable than previously presented. Therefore, many features and presentations need to be considered when evaluating a patient for SETD5 alterations through DES.

De novo variants in CDK13 associated with syndromic ID/DD: Molecular and clinical delineation of 15 individuals and a further review.

De novo variants in the gene encoding cyclin-dependent kinase 13 (CDK13) have been associated with congenital heart defects and intellectual disability (ID). Here, we present the clinical assessment of 15 individuals and report novel de novo missense variants within the kinase domain of CDK13. Furthermore, we describe 2 nonsense variants and a recurrent frame-shift variant. We demonstrate the synthesis of 2 aberrant CDK13 transcripts in lymphoblastoid cells from an individual with a splice-site variant. Clinical characteristics of the individuals include mild to severe ID, developmental delay, behavioral problems, (neonatal) hypotonia and a variety of facial dysmorphism. Congenital heart defects were present in 2 individuals of the current cohort, but in at least 42% of all known individuals. An overview of all published cases is provided and does not demonstrate an obvious genotype-phenotype correlation, although 2 individuals harboring a stop codons at the end of the kinase domain might have a milder phenotype. Overall, there seems not to be a clinically recognizable facial appearance. The variability in the phenotypes impedes an à vue diagnosis of this syndrome and therefore genome-wide or gene-panel driven genetic testing is needed. Based on this overview, we provide suggestions for clinical work-up and management of this recently described ID syndrome.

Diagnosis of warm dense conditions in foil targets heated by intense femtosecond laser pulses using Kα imaging spectroscopy.

Warm dense conditions in titanium foils irradiated with intense femtosecond laser pulses are diagnosed using an x-ray imaging spectroscopy technique. The line shapes of radially resolved titanium Kα spectra are measured with a toroidally bent GaAs crystal and an x-ray charge-coupled device. Measured spectra are compared with the K-shell emissions modeled using an atomic kinetics - spectroscopy simulation code. Kα line shapes are strongly affected by warm (5-40 eV) bulk electron temperatures and imply multiple temperature distributions in the targets. The spatial distribution of temperature is dependent on the target thickness, and a thin target shows an advantage to generate uniform warm dense conditions in a large area.

Deficient autophagy in microglia impairs synaptic pruning and causes social behavioral defects.

Autism spectrum disorders (ASDs) are neurodevelopmental disorders caused by various genetic and environmental factors that result in synaptic abnormalities. ASD development is suggested to involve microglia, which have a role in synaptic refinement during development. Autophagy and related pathways are also suggested to be involved in ASDs. However, the precise roles of microglial autophagy in synapses and ASDs are unknown. Here, we show that microglial autophagy is involved in synaptic refinement and neurobehavior regulation. We found that deletion of atg7, which is vital for autophagy, from myeloid cell-specific lysozyme M-Cre mice resulted in social behavioral defects and repetitive behaviors, characteristic features of ASDs. These mice also had increases in dendritic spines and synaptic markers and altered connectivity between brain regions, indicating defects in synaptic refinement. Synaptosome degradation was impaired in atg7-deficient microglia and immature dendritic filopodia were increased in neurons co-cultured with atg7-deficient microglia. To our knowledge, our results are the first to show the role of microglial autophagy in the regulation of the synapse and neurobehaviors. We anticipate our results to be a starting point for more comprehensive studies of microglial autophagy in ASDs and the development of putative therapeutics.

A natural infection by the red sea bream iridovirus-type Megalocytivirus in the golden mandarin fish Siniperca scherzeri.

An outbreak of a Megalocytivirus infection was found in the golden mandarin fish Siniperca scherzeri during September and October 2016, in Korea. Phylogeny and genetic diversity based on the major capsid protein (MCP) and adenosine triphosphatase (ATPase) genes showed a new strain. Designated as GMIV, this strain derived from the golden mandarin fish was suggested to belong to the red sea bream iridovirus (RSIV)-subgroup I. Additionally, this train clustered with the ehime-1 strain from red sea bream Pagrus major in Japan and was distinguished from circulating isolates (RSIV-type subgroup II and turbot reddish body iridovirus [TRBIV] type) in Korea. The infection level, evaluated by qPCR, ranged from 8.18 × 102 to 7.95 × 106  copies/mg of tissue individually, suggesting that the infected fish were in the disease-transmitting stage. The diseased fish showed degenerative changes associated with cytomegaly in the spleen as general sign of Megalocytivirus infection. The results confirm that the RSIV-type Megalocytivirus might have crossed the environmental and species barriers to cause widespread infection in freshwater fish.

Participation in school-related activities that require hand use for children with and without developmental disabilities.

BACKGROUND: Children with developmental disabilities (DD) may experience limited participation in school activities. Little is known about whether school participation of children with DD who attend special schools is impacted. This study specifically focused on physical engagement in school-related activities that require hand use for the comparison between this group of children with DD and typically developing children. METHODS: The sample consisted of 97 children with DD who attended special schools (mean age 8.2 ± 2.9 years; 60 boys and 37 girls) and 105 typically developing children who attended mainstream schools/kindergartens (mean age 8.6 ± 2.4 years; 48 boys and 57 girls). Parents completed the Children's Assessment of Participation with Hands, one of the domains of which captures participation in eight school-related activities involving hand use. RESULTS: Parents of children with DD reported that their children participated less, in terms of the number (χ2  = 8.45-14.97, P ≤ 0.004) and frequency (t = 4.00-6.47, P < 0.001), in four activities than typically developing children. Parents of children with DD also reported that more assistance was needed for their children's participation in all activities (t = 6.93-11.92, P < 0.001), and they wanted their children to participate in most activities more often and more independently (χ2  = 18.46-59.34, P < 0.001). CONCLUSIONS: Differences in participation in school-related activities requiring hand use between children with DD and typically developing children were revealed generally across all participation dimensions (does participate, frequency, independence, and desired change). This study provides information on the areas in which greater efforts are needed to support children's school participation.

De novo loss of function mutations in KIAA2022 are associated with epilepsy and neurodevelopmental delay in females.

Intellectual disability (ID) affects about 3% of the population and has a male gender bias. Of at least 700 genes currently linked to ID, more than 100 have been identified on the X chromosome, including KIAA2022. KIAA2022 is located on Xq13.3 and is expressed in the developing brain. The protein product of KIAA2022, X­linked Intellectual Disability Protein Related to Neurite Extension (XPN), is developmentally regulated and is involved in neuronal migration and cell adhesion. The clinical manifestations of loss­of­function KIAA2022 mutations have been described previously in 15 males, born from unaffected carrier mothers, but few females. Using whole­exome sequencing, we identified a cohort of five unrelated female patients with de novo probably gene damaging variants in KIAA2022 and core phenotypic features of ID, developmental delay, epilepsy refractory to treatment, and impaired language, of similar severity as reported for male counterparts. This study supports KIAA2022 as a novel cause of X­linked dominant ID, and broadens the phenotype for KIAA2022 mutations.

Association of the missense variant p.Arg203Trp in PACS1 as a cause of intellectual disability and seizures.

Graphical abstract key: ADHD, attention deficit hyperactivity disorder; ASD, atrial septal defect; DD, developmental delay; EEG, electroencephalogram; Ht, height; ID, intellectual disability; OCD, obsessive-compulsive disorder; OFC, open fontanelle; PDA, patent ductus arteriosis; PFO, patent foramen ovale; VSD, ventricular septal defect; Wt, weight.

Precision Control of the Electron Longitudinal Bunch Shape Using an Emittance-Exchange Beam Line.

We report on the experimental generation of relativistic electron bunches with a tunable longitudinal bunch shape. A longitudinal bunch-shaping (LBS) beam line, consisting of a transverse mask followed by a transverse-to-longitudinal emittance exchange (EEX) beam line, is used to tailor the longitudinal bunch shape (or current profile) of the electron bunch. The mask shapes the bunch's horizontal profile, and the EEX beam line converts it to a corresponding longitudinal profile. The Argonne wakefield accelerator rf photoinjector delivers electron bunches into a LBS beam line to generate a variety of longitudinal bunch shapes. The quality of the longitudinal bunch shape is limited by various perturbations in the exchange process. We develop a simple method, based on the incident slope of the bunch, to significantly suppress the perturbations.

Observation of Reverse Saturable Absorption of an X-ray Laser.

A nonlinear absorber in which the excited state absorption is larger than the ground state can undergo a process called reverse saturable absorption. It is a well-known phenomenon in laser physics in the optical regime, but is more difficult to generate in the x-ray regime, where fast nonradiative core electron transitions typically dominate the population kinetics during light matter interactions. Here, we report the first observation of decreasing x-ray transmission in a solid target pumped by intense x-ray free electron laser pulses. The measurement has been made below the K-absorption edge of aluminum, and the x-ray intensity ranges are 10^{16} -10^{17} W/cm^{2}. It has been confirmed by collisional radiative population kinetic calculations, underscoring the fast spectral modulation of the x-ray pulses and charge states relevant to the absorption and transmission of x-ray photons. The processes shown through detailed simulations are consistent with reverse saturable absorption, which would be the first observation of this phenomena in the x-ray regime. These light matter interactions provide a unique opportunity to investigate optical transport properties in the extreme state of matters, as well as affording the potential to regulate ultrafast x-ray free-electron laser pulses.

Navigation programs, are they helpful for perioperative care with thyroid cancer patients?

The purpose of this study was to develop and evaluate a navigation program for patients with thyroid cancer. The navigation program was developed following an analysis of the unmet needs of patients who underwent surgery for thyroid cancer. Ninety-nine patients in the control group received usual care, and 95 in the navigation group were managed with a navigation program during the perioperative period. The effectiveness of the navigation program was assessed by administering a questionnaire to both groups. Overall satisfaction scores were significantly higher in the navigation than in the control group (p = .025), as were satisfaction scores on the continuity of information (p < .001), the continuity of management (p = .002), the continuity of relationships with healthcare providers (p<.001), and patient empowerment (p < .001). The newly developed navigation program for patients with thyroid cancer was effective in raising satisfaction levels and in actively managing the disease during the perioperative period.